A Study to Evaluate the Efficacy and Safety of IV Peramivir in Addition to Standard of Care Compared to Standard of Care Alone in Adults and Adolescents Who Are Hospitalized Due to Influenza

This study has been terminated.

(This study was terminated for futility)

Sponsor:

BioCryst Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT00958776

First Posted: August 13, 2009

Last Update Posted: February 12, 2015

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A Phase 3, multicenter, randomized, double-blind, controlled study to evaluate the efficacy and safety of peramivir administered intravenously in addition to standard of care compared to standard of care alone in adults and adolescents who are hospitalized due to serious influenza.

A Phase 3, Multicenter, Randomized, Double-blind, Controlled Study to Evaluate the Efficacy and Safety of Peramivir Administered Intravenously in Addition to Standard of Care Compared to Standard of Care Alone in Adults and Adolescents Who Are Hospitalized Due to Serious Influenza

Time to Clinical Resolution (Kaplan-Meier Estimate) [ Time Frame: 10 days ]

Time to clinical resolution was defined as the time in hours from initiation of study treatment until normalization of at least 4 of the 5 signs within the respective normalization criteria, maintained for at least 24-hours. Time to clinical resolution was summarized by treatment group using the method of Kaplan-Meier. For subjects who did not experience clinical resolution, values were censored at the date of their last non-missing assessment of clinical resolution during the study (whether this assessment occurred as an inpatient or as an outpatient).

The reduction in viral shedding was assessed as the change from baseline in log10 tissue culture infective dose50 (TCID50/mL) and RT-PCR and was summarized for each treatment group and study visit.

Time to Alleviation of Clinical Symptoms of Influenza [ Time Frame: 10 days ]

Time to alleviation of clinical symptoms of influenza was measured as the time from the first dose of study drug through the time period in which all 7 symptoms of influenza (cough, sore throat, nasal congestion, myalgia [aches and pains], headache, feverishness, and fatigue) were absent or rated as no greater than mild for at least 24 hours. Time to alleviation of symptoms was estimated using the method of Kaplan-Meier. Subjects who did not have resolution of any individual clinical sign were censored at the time of their last non-missing assessment of that sign.

Time to Resolution of Fever (Kaplan-Meier Estimate) [ Time Frame: 10 days ]

Time to resolution of fever was measured as the time from initiation of study treatment until resolution of fever, maintained for at least 24 hours; temperature measurements taken less than 4 hours after antipyretic use were treated as missing values.

Time to Resumption of Usual Activities [ Time Frame: 10 days ]

Time to resumption of usual activities was determined from the visual analog scale (scale ranged from 0 to 10 where 0 indicated subject was unable to perform usual activities at all and 10 indicated subject was able to perform all usual activities fully). Time to resumption of usual activities was summarized by treatment group using the method of Kaplan-Meier.

Number of Subjects With ICU Admission [ Time Frame: 10 days ]

The number of subjects requiring ICU admission post-randomization was summarized by treatment group.

Duration of All ICU Admissions (Kaplan-Meier Estimate) [ Time Frame: 10 days ]

Duration of postbaseline ICU admission was defined as the total number of days in the ICU for those subjects who had a post-baseline admission to the ICU. Only days starting after the initial postbaseline admission were included. If a subject's stay in the ICU was ongoing, the duration was censored at the last study visit. Subjects who did not have a postbaseline admission had a duration of 0.

Other Outcome Measures:

Time to Hospital Discharge [ Time Frame: 10 days ]

Time to hospital discharge, defined as the number of days from initiation of study treatment until the subject was discharged from the hospital, was summarized by treatment group using the method of Kaplan-Meier. Subjects who were not discharged from the hospital were censored at their last study visit.

Incidence of Influenza-Related Complications [ Time Frame: 10 days ]

Influenza-related complications were defined as the occurrence of sinusitis, otitis, bronchitis, and pneumonia as reported on the influenza-related complications CRF.

Number of Subjects Requiring More Than 5 Days of Study Drug [ Time Frame: 10 days ]

Subjects who had not met the protocol-defined criteria of clinical resolution on Day 5 or who had detectable virus by RT-PCR from a sample collected on Study Day 4 after dosing continued their assigned treatment for a further 5 days.

Survival at 14 and 28 Days After Initiation of Study Drug (Kaplan-Meier Estimate) [ Time Frame: 28 days ]

Survival was calculated as the number of days from initiation of study drug until death or last contact. Estimates and 95% confidence intervals were calculated using the method of Kaplan-Meier and presented by treatment group.

Initial Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; IC50 (nM) [ Time Frame: Initial (baseline or post-baseline) and up to 10 days ]

Initial viral sensitivity to peramivir, oseltamivir, and zanamivir was assessed over time during the study, and was presented by influenza virus subtype. Initial assessment of susceptibility may have occurred at a post-baseline visit.

Change in Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; Fold Change From Initial [ Time Frame: Initial (baseline or post-baseline) and up to 10 days ]

Viral sensitivity to peramivir, oseltamivir, and zanamivir was assessed over time during the study, and was presented as fold change from initial sensitivity by influenza virus subtype. Initial assessment of susceptibility may have occurred at a post-baseline visit.

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Ages Eligible for Study:

12 Years and older (Child, Adult, Senior)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Age ≥12 years of age, male or female.

Able to provide informed consent, or for whom consent may be provided by guardian, unless informed consent provided by a guardian or a legally authorized representative is not consistent with applicable local or ethical concerns, procedures, directives and/or guidelines.

Subject must have at least one of the following clinical presentations at Screening:

Presence of at least one respiratory symptom (cough, sore throat, or nasal congestion) of any severity (mild, moderate, or severe).

Presence of at least one constitutional symptom (headache, myalgia, feverishness, or fatigue) of any severity (mild, moderate, or severe).

Onset of illness no more than 72 hours before presentation. Note: Time of onset of illness is defined as the earlier of either (1) the time when the temperature was first measured as elevated, OR (2) the time when the subject experienced the presence of at least one respiratory symptom AND the presence of at least one constitutional symptom.

Either:

Severity of illness that, in the Investigator's judgment, justifies hospitalization of the subject for supportive care.

Current history of congestive heart failure or angina. Presence of diabetes mellitus, clinically stable or unstable. Transcutaneous oxygen saturation <94% without supplemental oxygen for at least 5 minutes, or a medically significant decrease in oxygen saturation from an established baseline value (an investigative site at altitude >2000 ft above sea level will utilize different criteria for oxygen saturation).

Clinical Influenza with Positive Diagnostic Test. Subjects who have a positive rapid antigen test (RAT) for influenza A and/or influenza B (using a Sponsor-approved test kit), or positive test (using other methodology) for influenza A and/or B virus antigen or RNA performed in a clinical laboratory at the screening/enrollment evaluation are eligible for enrollment.

OR

Clinical Influenza with Negative Rapid Antigen Test (RAT). Subjects with a negative RAT test may be enrolled once the site has been approved by the Sponsor to enroll such subjects, based on documentation of an outbreak of influenza in the community. An influenza outbreak may be documented in the catchment area of the hospital via one of the following methods: 1) local confirmation of influenza A or B infection in the current influenza season by a) the institution's local laboratory, or b) the local public health system, or c) the national public health system, or d) a laboratory of a recognized multinational influenza surveillance scheme such as the European Influenza Surveillance Network (EISN); 2) prior enrollment of a RAT positive subject into this study at the same institution in the current influenza season.

Exclusion Criteria:

Subjects who have been hospitalized for greater than 24 hours (not including time spent in the Emergency Department).

Treatment with any dose(s) of rimantadine, amantadine, ribavirin, zanamivir, or oseltamivir in the previous 7 days.

Blood platelet count of < 20 x 109/L at the time of the screening evaluation.

Females who are pregnant (positive urine or serum pregnancy test at screening evaluation) or breastfeeding.

Actively undergoing systemic chemotherapy or radiotherapy treatment for a malignancy. Subjects who have completed treatment 30 days prior to enrollment are not excluded. Hormone treatment for cancer is also not excluded.

Presence of a pre-existing chronic infection that is undergoing or requiring medical therapy (eg, tuberculosis). Subjects with chronic osteomyelitis or Hepatitis B or C not requiring treatment are not excluded.

Presence of any pre-existing illness that, in the opinion of the investigator, would place the subject at an unreasonably increased risk through participation in this study.

Previous treatment with intravenous or intramuscular peramivir.

Participation as a subject in any study of an experimental treatment for any condition within the 30 days prior to the time of the screening evaluation.

Subjects diagnosed with Cystic Fibrosis.

Subjects with confirmed clinical evidence of acute non-influenzal infection at the time of screening evaluation.

Subjects who, in the judgment of the investigator, will be unlikely to comply with the requirements of this protocol.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00958776